title: Tobacco smoking effect on HIV-1 pathogenesis: role of cytochrome P450 isozymes.
abstract: BACKGROUND
  Tobacco smoking is highly prevalent among the HIV-1-infected population. In addition to diminished immune response, smoking has been shown to increase HIV-1 replication and decrease response to antiretroviral therapy, perhaps through drug-drug interaction. However, the mechanism by which tobacco/nicotine increases HIV-1 replication and mediates drug-drug interaction is poorly understood.
  
  
  METHODS
  In this review, the authors discuss the effects of smoking on HIV-1 pathogenesis. Since they propose a role for the cytochrome P450 (CYP) pathway in smoking-mediated HIV-1 pathogenesis, the authors briefly converse the role of CYP enzymes in tobacco-mediated oxidative stress and toxicity. Finally, the authors focus on the role of CYP enzymes, especially CYP2A6, in tobacco/nicotine metabolism and oxidative stress in HIV-1 model systems monocytes/macrophages, lymphocytes, astrocytes and neurons, which may be responsible for HIV-1 pathogenesis.
  
  
  CONCLUSIONS
  Recent findings suggest that CYP-mediated oxidative stress is a novel pathway that may be involved in smoking-mediated HIV-1 pathogenesis, including HIV-1 replication and drug-drug interaction. Thus, CYP and CYP-associated oxidative stress pathways may be potential targets to develop novel pharmaceuticals for HIV-1-infected smokers. Since HIV-1/TB co-infections are common, future study involving interactions between antiretroviral and antituberculosis drugs that involve CYP pathways would also help treat HIV-1/TB co-infected smokers effectively.
authors.affiliation: University of Missouri Kansas City, School of Pharmacy, Division of Pharmacology & Toxicology , Kansas City, MO 64108 , USA.
authors.forename: Anusha
authors.initials: A
authors.lastname: Ande
authors.forename: Carole
authors.initials: C
authors.lastname: McArthur
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000009:adverse effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects*; D014779:Virus Replication; D014026:Nicotiana
chemical_list: D044966:Anti-Retroviral Agents; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009538:Nicotine; D003577:Cytochrome P-450 Enzyme System; D011493:Protein Kinase C